synthesis of further divarinol and olivetol lichen para -depsides

Ausr. J . Chem., 1985, 38, 1863-71

Synthesis of Further Divarinol and Olivetol Lichen para-Depsides

John A. Elix, John L. Parker, Philip D. Tearne and Judith H. Wardlaw

Department of Chemistry, The Faculties, Australian National University, P.O. Box 4, Canberra, A.C.T. 2601.

Abstract

The lichen depsides 2-0-methyldivaricatic acid (I), 3-chlorodivaricatic acid (2), 4-0-demethylstenoporic acid (3), 2-0-methylstenosporic acid (4), 4-0-demethylimbricaric acid (5) and 3,5-dichloro- 2'-0-methylanziaic acid (6) have been prepared by unambiguous synthesis for the first time.

Introduction

Total synthesis has provided a definitive method for structural elucidation of lichen depsides and provides a useful alternative to the classical hydrolytic degrada- tion procedure.' Further, in cases where complex mixtures of homologous depsides or simply lack of lichen material make isolation of the depside impractical, chromatographic comparisons of synthetic material with the natural mixtures has enabled the identity of a number of new depsides to be e~ t ab l i shed .~ .~

In this paper we report the total synthesis of six lichen depsides, 2-0-methyldivaricatic acid 3-chlorodivaricatic acid (21,' 4-0-demethylstenoporic acid

' Elix, J. A., Whitton, A. A., and Sargent, M. V., Fortschr. Chem. Org. Narursr., 1984, 45, 104. Chester, D. O., and Elix, J. A., Aust. J. Chem., 1978, 31, 2745. Chester, D. O., and Elix, J. A., Aust. J . Chem., 1979, 32, 1399. Culberson, W. L., and Culberson, C. F., Occas. Pap. Farlow Herb. Cryptogam. Bot. Harv. Univ.,

1981, 16, 37. Huneck, S., Sundholm, G., and Follmann, G., Phytochemistry, 1980, 19, 645.

Short Communications

(3),6 2-0-methylstenosporic acid (4),4 4-0-demethylimbricaric acid (5)7 and 3,5-dichloro-2'-0-methylanziaic acid (6).8 The overall procedure, for such syntheses are now well establi~hed.~

4-0-Demethylstenosporic Acid (3) and 4-0-Demethylimbricaric Acid (5)

The two depsides (3) and (5) have been detected as components o<complex mixtures of homologous depsides in lichens of genus Neofuscelia6 and Cetrelia7 respectively. Neither compound was isolated but the respective structures were tentatively estab- lished by R, correlations in two dimensional thin-layer chroma tog ram^.'^ Subse- quently we have undertaken the synthesis of the depsides (3) and (5). The conden-

Pr FHII R I I

CSHI I Pr (11) (12)

sation of 4-benzyloxy-2-hydroxy-6-propylbenzoic acid (7)" with benzyl2,4-dihydroxy- 6-pentylbenzoate (9)9 and 2,4-dibenzyloxy-6-pentylbenzoic acid (8) with benzyl 2,4- dihydroxy-6-propylbenzoate in the presence of trifluoroacetic anhydride gave rise to benzyl 4-0-benzyl-4-0-demethylstenosporate (1 1) and benzyl 2,4-di-0-benzyl- 4-0-demethylimbricarate (12) respectively. Hydrogenolysis of the esters (1 1) and (12) in the presence of palladized carbon and hydrogen produced, in turn, 4-0-demethylstenosporic acid (3) and 4-0-demethylimbricaric acid (5). The thin layer-chromatographic behaviour of the latter compounds in three independent solvent systemst2 was

Culberson, C. F., Culberson, W. L., and Esslinger, T. L., Bryologist, 1977, 80, 125. ' Culberson, C. F. , and Culberson, W. L., Syst. Bot., 1976, 1, 325.

Huneck, S., Hofle, G., and Culberson, C. F., Phytochemistry, 1977, 16, 995. Elix, J. A., Aust. J. Chem., 1974, 27, 1767.

l o Culberson, C. F., and Johnson, A., J. Chromatogr., 1976, 128, 253. " Elix, J. A., and Norfolk, S., Ausr. J. Chem., 1975, 28, 399. I Culberson, C. F., J. Chromatogr., 1972, 72, 1 13.


identical to that of the corresponding unknown lichen depsides present in Neofuscelia puila (Ach.) Essl. and Cetrelia sanguinea (Schaer.) W. Culb. & C. Culb. This was further confirmed by high performance liquid chromatographic (h.p.1.c.) comparisons of the synthetic and natural compounds.

R' R' R' R~

OH (14) H Me CH2Ph Pr

(15) H Me CH2Ph C,H,,

Me0 OMe Me0 H H H Pr

2-0-Methyldivaricatic Acid (1) and 20-Methylstenosporic Acid (4)

The depsides 2-0-methyldivaricatic acid (1) and 2-0-methylstenosporic acid (4) were detected in extracts of the lichen Ramalina sayreana W. Culb. & C. Culb. by thin-layer chromatography (t.1.c.). The structure of these depsides followed after micro- hydrolysis of the crude extract and the identification of the hydrolysis products by comparative t.1.c. We have now completed an unambiguous synthesis of the depsides (1) and (4) and have confirmed their occurrence in R. sayreana by comparative t.1.c. and h.p.1.c. The condensation of 2,4-dimethoxy-6-propylbenzoic acid (13)13 with benzyl 2,4-dihydroxy-6-propylbenzoate (10) and benzyl 2,4-dihydroxy-6-pentylbenzoate (9) in the presence of trifluoroacetic anhydride gave rise to benzyl 2-0-methyldivaricatate (14) and benzyl2-0-methylstenosporate (15) respectively. Hydrogenolysis of the esters (14) and (15) in the usual manner produced 2-0-methyldivaricatic acid (1) and 2-0-methylstenosporic acid (4).

3-Chlorodivaricatic Acid (2)

The depside (2) was isolated from the lichen Thelomma mammosum5 and the structure was elucidated by 'H n.m.r. 13C n.m.r., mass and ultraviolet spectroscopy. 3-Chlorodivaricatic acid (2) is the only known monochlorodepside where the chlorine atom has substituted position 3. Direct chlorination of divaricatic acid (16) with sulfuryl chloride produced the corresponding 5-substituted isomer, 5-chlorodivaricatic acid (17). In fact, orsellinic acid derivatives are well known to undergo prefer- ential chlorination in the 5-position,14 so the foremost problem in any synthetic approach to the depside (2) is the synthesis of 3-chloro-2-hydroxy-4-methoxy-6-propylbenzoic acid (22) (Scheme 1). Chlorination of ethyl 4-hydroxy-2-0x0-6-propylcyclohex-3-ene-1-carboxylate (18) with two molar proportions of chlorine effected selective substitution and a r o r n a t i z a t i ~ n ' ~ ~ ~ ~ to afford ethyl 3-chloro-2,4-dihydroxy-6-propylbenzoate (19). No doubt this reaction proceeds by chlorination of the en01 (18) followed by elimination of hydrogen chloride from the dichloro

l3 Elix, J. A., and Norfolk, S., Aust. J. Chem., 1975, 28, 399. l4 Saniesson, J., Acta Chem. Scand., 1970, 24, 3373. l 5 Grossman, J. D., U.S. Pat. 3,701,801 (Chem. Abstr., 1973, 78, 3807q). l6 Fitzpatrick, L., Sala, T., and Sargent, M. V., J. Chem. Soc., Perkin Trans. 1 , 1980, 85. l7 Sargent, M. V., Vogel, P., and Elix, J. A., J. Chem. Soc., Perkin Trans. 1, 1975, 1986.


C02Et 2c1, @ - Me2S04 -

K2C03 HO HO Me0 OMe

(18) C1 c1

(19) (20)

Scheme 1

and subsequent oxidation (by a second chlorination-dehydrochlorination sequence). Methylation of the ester (19) by treatment with dimethyl sulfate and potassium carbonate gave ethyl 3-chloro-2,4-dimethoxy-6-propylbenzoate (20), and selective demethylation of this compound by treatment with boron trichloride gave ethyl 3-chloro-2-hydroxy-4-methoxy-6-propylbenzoate (21) in excellent yield. Subsequent hydrolysis of the ester (21) afforded the required key intermediate, 3-chloro-2-hydroxy- 4-methoxy-6-propylbenzoic acid (22).

The condensation of the acid (22) with benzyl 2,4-dihydroxy-6-propylbenzoate (10) in the presence of trifluoracetic anhydride gave rise to benzyl 3-chlorodivar- catate (23), and subsequent hydrogenolysis of this ester afforded 3-chlorodivaricatic acid (2).

This synthetic sample proved to be identical with the natural material.

3,5-Dichioro-2'-0-methylanziaic Acid (6)

The depside 3,5-dichloro-2'-0-methylanziaic acid (6) has been isolated from the lichen Lecanora sulphurella Hepp and its structure elucidated from spectroscopic data, hydrolysis and by partial synthesis of methyl 3,5-dichloro-2,2',4-tri-0-methylanziate (24).

We have now effected the synthesis of depside (6) starting from ethyl 2,4-dihydroxy-6-pentylbenzoate (25). Chlorination of the ester (25) with two molar proportions of sulfuryl chloride yielded ethyl 3,5-dichloro-2,4-dihydroxy-6-pentylbenzoate (26) and hydrolysis of this compound with concentrated sulfuric acid-water afforded 3,5-dichloro-6-pentylbenzoic acid (27). Condensation of the benzoic acid (27) and benzyl 4-hydroxy-2-methoxy-6-pentylbenzoate (28)' in the presence of trifluoroacetic anhydride gave the depside ester benzyl 3,5-dichloro-2'-0-methylanziate (29) in low yield. Hydrogenolysis of (29) under the usual conditions afforded 3,5-dichloro-2'-0- methylanziaic acid (6), identical in all respects with the natural material.


KoFoH C l w o q O M e

Me0 CO,CH,Ph Me0 OMe C02Me

CI Pr CI C 5 H ~ 1

(23) (24)

We attribute the low yield of (29) obtained in the condensation of (27)and (28) to self-condensation of the benzoic acid (27). In this case intramolecular hydrogen bonding between the Chydroxy group and the adjacent chlorine atoms is not partic- ularly strong and is thus ineffective in protecting this phenolic group from esterification.

Experimental

The general experimental details have been reported previo~sly.~

Ethyl 2,4-dibenzyloxy-6-pentylbenzoate

Ethyl 2,4-dihydroxy-6-pentylbenzoatem (2.5 g), anhydrous potassium carbonate and benzyl bromide (2.4 ml) were stirred and heated under reflux in acetone (40 ml) for 24 h. The mixture was poured into dilute cold hydrochloric acid and extracted with ether. The ethereal extract was washed with water, dried (MgSO,) and concentrated. The residue was distilled under reduced pressure to give ethyl 2,4-dibenzyloxy-6-pentylbenzoate (4.2 g, 98%) as a colourless liquid, b.p. 198O10.25 mm (Found: C, 76.8; H, 6.6. C28H3204 requires C, 77.1; H, 6.6%). 'H n.m.r. (CDCI,) 6 0.90, bt, (CH2),CH3; 1.15-1.90, m, 0CH2CH, and (CH2),CH3; 2.80, m, ArCH2; 4.41, q , J 7 Hz, 0CH2CH3; 5.10, s, 0CH2Ar; 6.51, s, ArH and 7.45, s, CoH5.

2,4- Dibenzyloxy-6-pentylbenzoic Acid (8)

A mixture of ethyl 2,4-dibenzyloxy-6-pentylbenzoate (2.5 g), potassium hydroxide (2.5 g), water (2.5 ml) and dimethyl sulfoxide (25 ml) was stirred and heated at 90" for 24 h. The solution was then poured into ice-cold hydrochloric acid and extracted with ether. The combined ethereal solution was washed with water and dried (MgSO,). Evaporation of this solution gave the acid (8)

' Korte, F., and Sieper, H., Justus Liebigs Ann. Chem., 1960, 630, 71.


(2.1 g, 90%) which was recrystallized from light petroleum to form colourless needles, m.p. 114" (Found: C, 76.6; H, 7.0. C26H2804 requires C, 76.5; H, 7.2%). 'H n.m.r. (CDCI,) 6 0.90, m, CH2CH3; 1.10-1.90, m, (CH,),CH,; 2.85, bt, ArCH,; 5.03, 5.09, 2s, OCH,; 6.41, s, ArH and 7.41, s, C6H5 Mass spectrum m/z 404 (M, 7%), 91 (100).

Ethyl 3-Chloro-2,4-dihydroxy-6-propylbenzoate (19)

A solution of chlorine (6.86 g) in glacial acetic acid (50 ml) was added dropwise to a stirred solution of ethyl 4-hydroxy-2-oxo-6-propylcyclohex-3-ene-l-carbo~ylate~~ (18) ( log) in glacial acetic acid (50 ml) at room temperature over a period of 45 min. The solution was then stirred at room temperature for a further 3 h and then heated at reflux for 16 h. The reaction mixture was cooled to room temperature, diluted with water (300 ml) and the precipitate filtered. The crude product was recrystallized from dichloromethane/light petroleum to give ethyl 3-chloro-2,4-dihydroxy- 6-propylbenzoate (19) (7.648, 67%) as colourless needles, m.p. 73" (Found: C, 55.7; H, 5.9; CI, 13.5. C12HlJC104 requires C, 55.7; H, 5.8; Cl, 13.7%). 'H n.m.r. (CDCI,) 6 0.90, bt, CH2CH2CH3; 1.25-1.90, m, 0CH2CH3 and CH2CH2CH3; 2.50-2.80, m, ArCH,; 4.50, q, J 7 Hz, OCHZ; 6.17, s, OH; 6.57, s, ArH and 12.77, s, bonded OH. Mass spectrum mlz 258 (M, 16%), 212 (100).

Ethyl 3-Chloro-2,4-dimethoxy-6-propylbenzoate (20)

Ethyl 3-chloro-2,4-dihydroxy-6-propylbenzoate (19) (5,0g), anhydrous potassium carbonate (15 g) and dimethyl sulfate (4.88 g, 4.0 ml) were stirred and heated under reflux in acetone (100 ml) for 24 h. The mixture was poured into dilute cold hydrochloric acid and extracted with ether. The ethereal phase was washed with water, dried (MgSO,) and the solvent removed. The ester (20) (5.54 g, 99%) was obtained as a colourless oil. A portion was purified on a Chromatron with 20% ethyl acetatellight petroleum as eluent and obtained as a colourless oil (Found: C, 58.5; H, 6.5; C1, 12.6. C14H19C104 requires C, 58.6; H, 6.6; CI, 12.4%). 'H n.m.r. (CDCI,) 6 0.90, m, CH2CH2CH3; 1.25-1.90, m, CH2CH2CH3 and 0CH2CH3; 2.50-2.80, m, ArCH,; 4.00, S, OMe; 4.45, q, J 7 Hz, OCH,; 6.67, s, ArH. Mass spectrum mlz 286 (M, 35%), 225 (100).

Ethyl 3-Chloro-2-hydroxy-4-methoxy-6-propylbenzoate (21)

A solution of boron trichloride (5.12 g) in dichloromethane (20 ml) was added dropwise to a stirred solution of ethyl 3-chloro-2,4-dimethoxy-6-propylbenzoate (20) (4.0 g) in dichloromethane (30 ml) at -80". After the addition, stirring was continued as the reaction mixture was slowly warmed to room temperature. The reaction mixture was then poured into water, extracted with ether and the ethereal solution washed with water and dried (MgSO,). On removal of the ether the residue was crystallized from dichloromethane/light petroleum to give ethyl 3-chloro-2-hydroxy- 4-methoxy-6-pentylbenzoate (21) (3.6 g, 95%) as colourless needles, m.p. 79" (Found: C, 57.3; H, 6.3; CI, 13.1. CI3Hl7C1O4 requires C, 57.3; H, 6.3; Cl, 13.0%). 'H n.m.r. (CDCI,) 6 0.97, bt, CH2CH2CH3; 1.15-2.25, m, 0CH2CH3 and CH2CH2CH3; 2.96, bt, ArCH,; 4.00, s, OMe; 4.47, q, J 7 Hz, OCH,; 6.40, s, ArH and 12.53, s, OH. Mass spectrum mlz 272 (M, 13%), 226 (100).

3-Chloro-2-hydroxy-4-methoxy-6-propylbenzoic Acid (22)

A solution of ethyl 3-chloro-2-hydroxy-4-methoxy-6-propylbenzoate (21) (1.0 g), potassium hydroxide (0.5 g) and water (3.0 ml) in ethanol (50 ml) was boiled under reflux for 24 h. The mixture was poured into cold dilute hydrochloric acid and extracted with several portions of ether. The combined ether solution was extracted with a saturated sodium hydrogen carbonate solution. The aqueous phase was reacidified and extracted with ether. This ethereal phase was dried (MgSOA the solvent evaporated and the residue recrystallized from ethyl acetatellight petroleum to give 3-chloro-2-hydroxy-4-methoxy-6-propylbenzoi acid (22) (22%) as colourless crystals, m.p. 217" (Found: C, 54.2; H, 5.5. CllH13C104 requires C, 54.0; H, 5.4%). 'H n.m.r. (CDCI,) 6 0.95, bt, CH2CH3; 1.25-1.90, m, CH2CH3; 3.00, bt, ArCH2; 4.00, s, OMe; 6.39, s, ArH and 13.27, bs, OH and C02H. Mass spectrum mlz 244 (M, 1 .5 %), 172 (100).

l9 Sonn, A., Ber. Dtsch. Chem. Ges., 1928, 61, 2479; 1931, 64, 1851.


Ethyl 3,5-Dichloro-2,4-dihydroxy-6-pentylbenzoat (26)

A solution of sulfuryl chloride (3 ml) in anhydrous ether was added dropwise to a stirred solution of ethyl 2,4-dihydroxy-6-pentylbenzoate (25)" (3.9g) in anhydrous ether (60ml) at room temperature. Stirring was continued for 12 h and then the solvent was removed under reduced pressure. The residue so obtained was crystallized from cyclohexane to give the dichloro ester (26) (4.32 g, 87%) as colourless crystals, m.p. 73-75" (Found: C, 52.2; H, 5.6. Cl4Hl8CI2O4 requires C, 52.4; H, 5.7%). 'H n.m.r. (CDC13) 6 0.92, bt, (CH2)4CH3; 1.30-1.66, m, 0CH2CH3 and (CH2),CH3; 3.16, bt, ArCH2; 4.52, q, J 7 Hz, OCH,; 6.60,12.44,2s, OH. Mass spectrum mlz 320 (M, 273,273 (100).

3,5-Dichloro-2,4-dihydroxy-6-pentylbenzoi Acid (27)

Ethyl 3,5-dichloro-2,4-dihydroxy-6-pentylbenzoate (0.68 g) (26) was dissolved in concentrated sulfuric acid (7 ml) at 0°, and the solution maintained at this temperature for 24 h. The reaction mixture was then diluted with cold water, and extracted with ether. The ethereal phase was washed repeatedly with saturated sodium hydrogen carbonate solution. The combined washings were then reacidified and extracted with several portions of ether. The ethereal phase so obtained was dried (MgS04) and the solvent removed under reduced pressure. The residue obtained was crystallized from hexane to give 3,5-dichloro-2,4-dihydroxy-6-pentylbenzoic acid (27) (0.49 g, 79 %) as colourless needles, m.p. 130-131" (lit.' 131-132") (Found: C, 48.8; H, 4.8. Calc. for C12H14C1204: C, 49.2; H, 4.8%).

Synthesis of Depsides-General Procedure

The appropriate carboxylic acid, i.e. (7), (a), (13), (22), (27) (1 mmol), and benzyl ester i.e. (9), (lo), (28) (1 mmol), were dissolved in a solution of anhydrous toluene (4 ml) and trifluoroacetic anhydride (1 ml) and permitted to stand at room temperature for 2 h. The solvent was then removed under reduced pressure and the residue adsorbed on a thick-layer plate. Elution with 20% ethyl acetatellight petroleum generally developed two major bands; the faster-moving depside ester and the slower unchanged benzyl ester. The former band was removed and extracted with ethyl acetate. Removal of the solvent gave the respective depside esters. The depside ester, i.e. (ll), (12), (14), (1 5), (23), (29) (0.5 mmol), was dissolved in ethyl acetate (5 ml) containing 10 % palladium-on- carbon (25 mg), and the suspension was stirred in an atmosphere of hydrogen for 2 h. The catalyst was then filtered and the solvent evaporated. The depside so obtained was recrystallized from an appropriate solvent.

4-(2',4'-Dimethoxy-6'-propylbenzoyloxy)-2-hydroxy-6-propylbenzoic Acid (2-0-Methyldivaricatic Acid) (I)

Benzyl 2-0-methyldivaricatate (14) (20%) crystallized from n-pentane in colourless needles, m.p. 79" (Found: C, 71.2; H, 6.6. C29H3207 requires C, 70.7; H, 6.6%). 'H n.m.r. (CDCI,) 60.76, 0.97, 2 bt, J 7 H z , CH2CH3; 1.18-1.90, m, CH2CH3; 2.75, 2.90, 2 bt, J 7 H z , ArCH,; 3.88, s, OMe; 5.47, s, OCH,; 6.49, s, H3, H5; 6.70, 6.88, 2d, J 2 .5 Hz, H3', H5'; 7.56, s, C6H5 and 11.71, s, OH. Mass spectrum m/z 492 (M, O.5%), 207 (100).

2-0-Methyldivaricatic acid (1) (61 %) crystallized from cyclohexane in colourless needles, m.p. 118" (Found: C, 65.6; H, 6.5. C22H2607 requires C, 65.6; H, 6.5%). 'H n.m.r. (CDCI,) G 1.00, bt, J 7.0 Hz, CH2CH3; 1.40-2.05, m, CH2CH3; 237-3.22, m, ArCH,; 3.88, 3.91, 2s, OMe; 6.43, s, H 3, H5; 6.70,6.88,2d, J 2 . 5 Hz, H 3', H5'; and 10.50, bs, C 0 2 H and OH. Mass spectrum mlz 302 (0.6%), 224 (9), 208 (13), 207 (loo), 196 (lo), 191 (13), 178 (20), 152 (lo), 150 (6), 137 ( 5 ) , 124 (15), 123 (9), 121 (7). The t.l.c.12 and h.p.1.c. behaviour of synthetic (1) was identical with that of a minor metabolite of Ramalina sayreana W. Culb. & C. Culb.

4(2',4'-Dimethoxy-6'-propylbenzoyloxy)-2-hydroxy-6-pentylbenzoic Acid (2-0-Methylstenosporic Acid) (4)

Benzyl 2-0-methylstenosporate (15) (17 %) was recrystallized from n-pentane to give colourless crystals, m.p. 76" (Found: C, 71.9; H, 7.0. C31H3607 requires C, 71.5; H, 7.0%). 'H n.m.r. (CDC13) 6 0.67-1.00, m, CH2CH3; 1.00-1.90, m, (CH2)3 and CH2CH2CH3; 2.48-2.92, m,


ArCH,; 3.87, 3.90, 2s, OMe; 5.44, s, 0 C H 2 ; 6.44, s, H3, H5; 6.68, 6.80, 2d, J 2.5 Hz, H3', H5'; 7.52, s, CsH5; 11.78, s, OH. Mass spectrum m/z 520 (M, 0.3%), 207 (loo).*

2-0-Methylstenosporic acid (4) (50%) crystallized from cyclohexane as colourless, rod-shaped crystals, m.p. 112" (Found: C, 67.0; H, 7.0. C24H3007 requires C, 67.0; H, 7.0%). 'H n.m.r. (CDCI,) 6 0.75-1.13, m, CH2CH3; 1.13-1.96, m, (CH2)3CH3 and CH2CH2CH3; 2.70, bt, J 7.5 Hz, ArCH2; 2.85-3.22, m, ArCH,; 3.87, 3.90, 2s, OMe; 6.42, s, H3, H5; 6.76, 6.82, 2d, J 2 . 5 Hz, H3', H5'; 10.65, bs, C 0 2 H and OH. Mass spectrum m/z 386 (0.1 %), 224 (I), 208 (13), 207 (loo), 191 (2), 177 (2). The t.l.c.12 and h.p.1.c. behaviour of synthetic (4) was identical with that of the major metabolite of Ramalina sayreana W. Culb. & C. Culb.

4-(2',4'-Dihydroxy-6'-propylbenzoyloxy)-2-hydroxy-6-pentylbenzoic Acid (4-0-Demethylstenosporic Acid) (3)

Benzyl4-0-benzyl-4-0-demethylstenosyorate (1 1) (59 %) was recrystallized from light petroleum/ dichloromethane to form colourless needles, m.p. 108" (Found: C, 74.4; H, 6.7. C36H3807 requires C, 74.0; H, 6.9%). 'H n.m.r. (CDCI3) 6 0.80-1.00, m, CH2CH3; 1.05-2.02, m, (CH2)3CH3 and CH2CH2CH3; 2.70-3.10, m, ArCH,; 5.08, 5.40, 2s, OCH,; 6.50, s, H 3, H5; 6.55, 6.75, 2d, J 2.5 Hz, H 3', H5'; 7.50, s, C6H5. Mass spectrum m/z 223 (13), 91 (100).

4-0-Demethylstenosporic Acid (3) (98 %) crystallized from light petroleum/acetone to form colourless prisms, m.p. 108" (Found: C, 65.8; H, 6.6; C22H2607 requires C, 65.7. H, 6.5%). 'H n.m.r. (D3COCD3) 6 0.97, m, CH2CH3; 1.17-2.10, m, and CH2CH2CH3; 2.73-3.27, m, ArCH2; 6.37, 6.47, 2d, J 2.5 Hz, H3', H5'; 6.83, s, H3, H5. Mass spectrum m/z 224 (24%), 206 (38), 196 (19), 181 (20), 178 (63), 168 (22), 163 (16), 150 (61), 137 (14), 124 (loo), 123 (33), 122 (23) and 121 (32). The t.l.c.12 and h.p.1.c. behaviour of synthetic (3) was identical with that of a minor metabolite of Neofirscelia pulla (Ach.) Essl.

4-(2',4'-Dihydroxy-6'-pentylbenzoyloxy)enzoic Acid (4-0- Demethylimbricaric Acid) (5)

Benzyl2,4-di-0-benzylimbricarate (12) (65 %) crystallized from dichloromethane/light petroleum as colourless needles, m.p. 105.5-106" (Found: C, 77.1 ; H, 6.6. C43H4407 requires C, 76.8; H, 6.6%). 'H n.m.r. (CDCI,) 6 0.87, m, CH2CH3; 1.00-1.84, m, (CH2)$2H3 and CH~CHZCHJ; 2.60-2.85, m, ArCH,; 5.08, 5.35, 2s, OCH,; 6.48, s, H3, H5; 6.37, 6.65, 2d, J 2.5 Hz, H 3', H5'; 7.38, s, C6H5. Mass spectrum mlz 236 ( l l ) , 235 (68), 91 (100).

4-0-Detnethylimbricaric Acid (5) (92%) crystallized from light petroleum/acetone in colourless prisms, m.p. 108" (Found: C, 66.0; H, 6.6. C2,HZ6O7 requires C, 65.7; H, 6.5%). 'H n.m.r. (CDC13/(CD3)2SO) 6 0.97, m, CHZCH3; 1.07-2.00, m, (CH2),CH3 and CHZCH2CH3; 2.86-3.20, m, ArCH,; 6.33,6.43,2d, 1 2 . 5 Hz, H 3', H5'; and 6.81, s, H 3, H5. Mass spectrum mlz 224 (2%), 196 (36), 179 (14), 178 (loo), 152 (48), 150 (39, 137 (22), 125 (13), 124 (97), 123 (51), 122 (19) and 121 (32). The t.1.c." and h.p.1.c. behaviour of synthetic (5) was identical with that of a minor metabolite of Cetrelia sanguinea (Schaer.) W. Culb. & C. Culb.

4-(3'-Chloro-4'-methoxy-2'-hydroxy-6'-propyezoyoxy)-2-hydroxy-6-propylbenzoic Acid (3-Chloro- diuaricatic Acid) (2)

Benzyl 3-chlorodivaricatate (23) (36%) was obtained as a colourless oil. 'H n.m.r. (CDC13) 6 0.97, bt, CH2CH3; 1.20-2.19, m, CH2CH3; 3.00, bt, ArCH,; 4.03, s, OMe; 5.50, s, OCH2; 6.51, s, H5; 6.63, 6.80, 2d, J 2 .5 Hz, H3', H5'; 7.53, s, C6H5. Mass spectrum mlz 286 (lo%), 91 (100).

3-Chlorodiv~ricatic acid (2) (97 %) crystallized from ethyl acetatellight petroleum as c o l o ~ r l e s ~ crystals, m.p. 169' (lit.' 159-160") (Found: C, 59.1 ; H, 5.4. Calc. for Cz1Hz3C107: C, 59.6; H, 5.5%). 'H n . m ~ . ~ [CDC13/(CD3),SO] 60.98, bt, CH2CH3; 1.25-1.90, m, CH2CH3; 2.91-3.15, bt, ArCH,; 3.98, s, OMe; 6.44, s, H5; 6.62, 6.74, 2d, J 2.5 Hz, H 3', H5'. Mass spectrum5 mlz 334 (1 %), 244 (I), 227 (8), 226 (12), 202 (16), 196 (2), 185 (17), 178 (8), 174 (27), 173 (31A 172 (83), 171 (77), 152 (50), 138 ( l l ) , 137 (38), 124 (loo), 123 (62).

* Note that in the trivial names of the depsides the atoms on the 'left' side of the molecule are left unprimed, whereas in systematic names they are primed. Trivial nomenclature has been followed for n.m.r. assignments.

Short Communications 1871

4-(3',5'-Dichloro-2',4'-dihydroxy-6'-pentylbenzoyloxy)-2-rnethoxy-6-pentylbenzoi~ Acid (3J-Dichloro- 2'-0-methylanziaic Acid) (6)

Benzyl 3,5-dichloro-2'-0-methylanziate (29) (48%) was obtained as a colourless oil. 'H n.m.r. (CDCI,) 6 0.78-0.98, m, CH2CH3; 1.14-1.82, m, (CH2)3CH3; 2.52, 3.20, 2bt, J 7 Hz, ArCH,; 3.83, s, OMe; 5.41, s, OCH,; 6.28, s, OH; 6.62, 6.66, 2d, J 2 Hz, H3', H5'; 7.38-7.60, m, C6H5.

3,5-Dichloro-2'-0-methylanziaic acid (6) (90%) crystallized from acetone/benzene in colourless needles, m.p. and m.m.p. 153-155" (lit.' 154-155)" (Found: C, 58.2; H, 5.9. Calc. for CzsH3,C1207: C, 58.5; H, 5.9%). 'H n.rn.r.' (CDC13) 6 0.89, bt, J 7 Hz, CH2Cf-I,; 1.24-1.84, m, (CHZ),CH3 2.76, 3.22, 2bt, J 7 Hz, ArCH2; 3.91, s, OMe; 6.68, 6.77, 2d, J 2 Hz, H3', H5'; 11.70, bs, C 0 2 H and OH. Mass spectrums mlz 279 (3 %), 182 (100).

Acknowledgments

We wish to thank Dr Siegfried Huneck, Halle, for generous samples of natural 3-chlorodivaricatic acid and 3,5-dichloro-2-'0-methylanziaic acid and Dr C. F. Culberson, Duke University, Durham, N.C. for her cooperation in providing a small specimen of Ramalina sayreana.

Manuscript received 25 June 1985

synthesis of further divarinol and olivetol lichen para -depsides

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